The aim of this project is to study the control of antibody production by antigen specific regulatory T lymphocytes, idiotype-specific antibodies and T cells, and tolerogenic antigens. The effects of these agents will be examined on physiologic antibody responses, and on the function of antigen-binding plasmacytoma cell lines which are more amenable to detailed biochemical and morphologic analyses. The possibility that syngeneic antigen-specific cytolytic T lymphocytes (CTL) have an immunoregulatory function will be assessed by determining the effect of hapten (e.g. TNP)-specific CTL on anti-TNP antibody responses and on the TNP-binding Balb/c plasmacytoma, MOPC 315. The possible presence of hapten-specific suppressor T cells will be critically evaluated. The locus of action of such CTL or suppressor cells will be analyzed, in terms of their cellular target and the histocompatibility determinants they recognize. Idiotype-specific effector and suppressor T cells will be generated by appropriately immunizing syngeneic mice with pure myeloma proteins, and their effects on myeloma growth and function tested. Effector and suppressor T cells specific for the TEPC 15 idiotype will be examined for their effect on antibody responses to phosphorylcholine in Balb/c mice, since such responses are oligoclonal, with the TEPC15 idiotype being the major constituent. The effects of anti-idiotypic antibodies on myeloma growth and function, and the mechanisms of idiotype-specific resistance to myeloma growth will be investigated in vitro. Finally, we will continue our studies on inhibition of myeloma function induced by tolergenic antigens in vitro by determining the fate of suppressive and non-suppressive antigens after their interactions with the cells, and by studying this phenomenon with different cell lines. Pursuing the hypothesis that intracellular ligand persistence may be important in tolerance induction, the fate of anti-immunoglobulin antibodies in adult B lymphocytes and tolerance-susceptible neonatal B cells will be compared.